As with other posts from the UC Davis CRISPR meeting, since I was taking notes on the fly during this session, this post is a stream of bits from the different talks, often trying to capture the essence of key questions or ideas as the speakers talked so forgive the format.

Overall from this session, the potential future somatic-gene therapy kind of use of CRISPR for catastrophic, fatal diseases such as Huntington’s Disease is something that needs special attention and discussion. More data is needed to know how this will play out.

Jacob Corn is a pioneering CRISPR scientist at IGI at Berkeley. I thought it was really cool that he passed a model of CRISPR-Cas9 around for audience. He made the analogy that what we are doing as a field is kind of like driving a car while still working on the car. It was striking when he pointed out the massive increase in publications on CRISPR-Cas9 going from 1 original paper in something like a year to start to now an average of 6 papers per day.

Kyle Fink. Kyle is a Huntington’s Disease (HD) researcher here at UC Davis, focusing on genetic approaches to HD including using CRISPR for somatic targeting. He gave an overview of HD and discussed targeting CAG repeats. A team could target the mutant HD DNA, RNA or the toxic protein itself. Targeting DNA could be more effective. Can we truncate the CAG repeats with CRISPR or other similar methods? Or could we silence the expression of the mutant allele specifically. We could use a combo of stem cell and gene therapy. I was impressed by the work he’s doing.

Vicki Wheelock. Dr. Wheelock is a UC Davis physician who cares for HD patients and also conducts research. She provided a very powerful perspective. HD manifests earlier than other neurodevelopmental diseases, typically in 30s and 40s at the peak of life. There are 30,000 cases in the US, but ripple effect affects a lot more people negatively. HD has many, diverse, and often tragic symptoms via the striatum being injured in HD. All treatments are now palliative. Stem cell therapies bring hope for replacement therapy such as MSCs with BDNF (which is taken out by HD). Another example is anti-sense oligo (ASO), which is the basis of a trial via spinal taps in Canada now. But ASO is not specific to mutant HD allele so need data on safety. She highlighted the huge unmet need. I learned something else new about HD in this talk in that HD families went underground during the eugenics movement. There is a stigma, but fortunately that is decreasing. Still a need for other new technologies such as CRISPR.

Judy Roberson. Judy is a wonderful patient advocate for the HD community for over 20 years and has served for 5 years on an FDA advisory panel. She was the first voting HD advocate on that panel. Part of the title of her talk was “HD: The Perfect First Model for CRISPR.” She gave a very moving talk.

She talked about how HD hit her family like a ton of bricks. Her MIL was affected in 30s. Took a long time for diagnosis and died at age 55. She and her husband Tim have 4 children. Tim’s brother Joe died of HD at 52. Judy’s husband was diagnosed at 39 and died in his early 50s. People with HD are often underground and there are worries about genetic discrimination. The stigma remains.

Judy talked about the unique HD program at UC Davis that has more than 500 patients. Some patients move here to be part of the program.

I was impressed with her guts and bluntness. For instance, she criticized the FDA for a number of reasons including lack of listening to patients and their overly conservative approach.

She also had some words for CIRM. “I love CIRM”, she said, but they urgently need some changes including more transparency and more of a role for patient advocates at each step. Judy wrapped up by invoking CRISPR as a “magic scissors” to tackle the mutant HD allele.

The panel also answered questions after they each spoke. For instance, I asked them about the potential use of CRISPR in human embryos to prevent HD.

Hi Paul- at the patient-focused FDA meeting on Parkinson’s disease and HD last year, there was a discussion about using CRISPER for HD.
The consensus was that there are already well-established technologies that could drastically reduce the disease in just a few generations.
The best current solution would be to increase the accessibility of genetic testing and figure out how to get insurance coverage for IVF and PGD. Imagine how much difference it would make if testing for trinucleotide length in the HTT gene was a cheap test, and IVF/PGD were available to those at risk.